NBM-HD-3, a novel histone deacetylase inhibitor with anticancer activity through modulation of PTEN and AKT in brain cancer cells

Wei Jan Huang, Chia Wei Lin, Chi Yun Lee, Li Ling Chi, Yi Chen Chao, Hsien Ning Wang, Bi Lian Chiou, Tzu Jung Chen, Chung Yang Huang, Chia Nan Chen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Ethnopharmacological relevance: Taiwanese green propolis (TGP) extract contains a variety of chemical components and has proven to have broad-spectrum biological activities, including anticancer, antioxidant, and antimicrobial activities. Propolin G, an active anticancer component of TGP, was isolated and characterized in this study. Histone deacetylase inhibitors (HDACis) have been shown to be effective anticancer agents. The aim of this study was to develop a novel HDACi and investigate its anticancer mechanism. Materials and methods: NBM-HD-3, a novel HDACi, was derived from propolin G. Two brain cancer cell lines (c6 and DBTRG-05MG) were used in the anti-proliferation assay. NBM-HD-3 treated cells were analyzed by flow cytometry in the cell cycle assay. The gene expression of NBM-HD-3 treated cells was determined by real-time quantitative PCR. HDAC enzyme assay, confocal microscopy and Western blot assay were used to validate NMB-HD-3 as HDACi. Western blot assay was used for analyzing cell cycle modulation by PTEN and AKT. Results: NBM-HD-3 was found to have potent anti-proliferative activity in brain cancer cells (rat C6 glioma and human DBTRG-05MG glioblastoma). Western blot analysis and HDAC enzyme assay indicated that NBM-HD-3 was an HDAC inhibitor. The Western blot data exhibited increased levels of p21, Ac-histone 3, Ac-histone 4, and Ac-tubulin after brain cancer cells being treated with NBM-HD-3. NBM-HD-3 also affected the cell cycle regulators such as p21 and cyclin B1. In the study for its anticancer mechanism, NBM-HD-3 was found to increase PTEN and AKT protein levels significantly, while decreasing p-PTEN and p-AKT levels markedly. Conclusion: This study demonstrated that the novel compound, NBM-HD-3, is a potent HDAC inhibitor. It produces anticancer activity through modulation of PTEN and AKT in brain cancer cells.

Original languageEnglish
Pages (from-to)156-167
Number of pages12
JournalJournal of Ethnopharmacology
Volume136
Issue number1
DOIs
Publication statusPublished - Jun 14 2011

Fingerprint

Histone Deacetylase Inhibitors
Brain Neoplasms
Western Blotting
Propolis
Cell Cycle
Enzyme Assays
Histones
PTEN Phosphohydrolase
Cyclin B1
6-(3-hydroxy-3-methylbutyl)-2'-(7-hydroxy-3,7-dimethyloct-3-enyl)-3',4',7-trimethoxyflavanone
Tubulin
Glioblastoma
Confocal Microscopy
Glioma
Antineoplastic Agents
Real-Time Polymerase Chain Reaction
Flow Cytometry
Antioxidants
Gene Expression
Cell Line

Keywords

  • AKT
  • Histone deacetylase inhibitor
  • NBM-HD-3
  • PTEN
  • Taiwanese green propolis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

NBM-HD-3, a novel histone deacetylase inhibitor with anticancer activity through modulation of PTEN and AKT in brain cancer cells. / Huang, Wei Jan; Lin, Chia Wei; Lee, Chi Yun; Chi, Li Ling; Chao, Yi Chen; Wang, Hsien Ning; Chiou, Bi Lian; Chen, Tzu Jung; Huang, Chung Yang; Chen, Chia Nan.

In: Journal of Ethnopharmacology, Vol. 136, No. 1, 14.06.2011, p. 156-167.

Research output: Contribution to journalArticle

Huang, Wei Jan ; Lin, Chia Wei ; Lee, Chi Yun ; Chi, Li Ling ; Chao, Yi Chen ; Wang, Hsien Ning ; Chiou, Bi Lian ; Chen, Tzu Jung ; Huang, Chung Yang ; Chen, Chia Nan. / NBM-HD-3, a novel histone deacetylase inhibitor with anticancer activity through modulation of PTEN and AKT in brain cancer cells. In: Journal of Ethnopharmacology. 2011 ; Vol. 136, No. 1. pp. 156-167.
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AU - Chao, Yi Chen

AU - Wang, Hsien Ning

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AU - Huang, Chung Yang

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